Dose intensity is critical in the treatment of these tumors. To facilitate maximum dosing of chemotherapeutic agents, anticipatory supportive care is necessary. Neutrophils are stimulated with G-CSF, and fevers are aggressively treated. New symptoms that occur while patients are being treated should be closely evaluated and monitored.

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Antineoplastic Agents

Class Summary

Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect it. After cells divide, they enter a period of growth (G1 phase), followed by DNA synthesis (S phase). The next phase is a premitotic phase (G2 phase), after which comes the final phase, mitotic cell division (M phase).

Rates of cell division vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant ones do. This is partly the rationale for current cyclic dosage schedules.

Etoposide is a glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect by stabilizing normally transient covalent intermediates formed between DNA substrate and topoisomerase II. This results in single- and double-strand DNA breaks.

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Uroprotectants

Class Summary

Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide or cyclophosphamide. In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity.

Samuel Gross, MD Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University